ALL, Recurrent, Adult, AML, Adult Recurrent, MDS
Conditions
Keywords
TCR, T-cell therapy
Brief summary
The goal of this clinical trial is to test BSB-1001 which is a new type of cellular therapy to treat blood cancers (AML, ALL and MDS). It will evaluate the safety of BSB-1001 and also determine whether it works to prevent relapse of your cancer.
Detailed description
This is a first-in-human, multicenter, open-label, dose-finding study for the evaluation of an HA-1 minor histocompatibility antigen (miHA)-reactive TCR-modified T cell product (BSB-1001) derived from an HLA-matched allogenic donor, in patients with AML, ALL or MDS undergoing an HLA-matched alloHSCT who are at a high risk for relapse post-HSCT. BSB-1001 targets the HLA-A\*02:01-restricted HA-1 miHA. Enrolled patients must be HLA-A\*02:01 and HA-1-positive (H/H or H/R), with an identified HLA-matched, HA-1-negative (R/R) donor. Patients will undergo one of the following myeloablative conditioning regimens, according to standard institutional procedures, which include either fludarabine+thiotepa+total body irradiation, or busulfan+ melphalan+ fludarabine. After conditioning is completed, patients will receive the CD34-selected alloHSCT followed by BSB-1001 on day 0, without any prophylactic immunosuppression. The study is an adaptive dose escalation design with 1 to 3 cohorts to evaluate single doses of BSB-1001. Three to six patients will be enrolled in each cohort and enrolled patients will be followed until completion of the study. If the maximum tolerated dose (MTD) is reached or if a dose is deemed promising, the Sponsor may determine to either cease enrollment or open an expansion cohort at the desired dose level. The optional expansion part of the study is planned to include approximately 20 additional AML patients at the recommended dose.
Interventions
DRUGSOC + BSB-1001 Dose Escalation Cohort
Patients will receive BSB-1001 a single intravenous (IV) infusion on day 0 following the infusion of the CD34-allo hematopoietic stem cell transplant (HCT).
DRUGSOC+BSB-1001 Expansion Dose
Patients will receive BSB-1001 a single intravenous (IV) infusion on day 0 following the infusion of the CD34-allo hematopoietic cell transplant (HCT).
Sponsors
BlueSphere Bio, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, ages 18 - 70 years inclusive, undergoing alloHCT. 2. Any of the following high-risk hematologic malignancies: 1. AML diagnosed which has been treated with at least two lines of therapy\* Refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high-risk disease For patients in remission meeting criteria a, consolidation regimens would be considered another line of therapy of eligibility purposes 2. ALL which has been with abnormal lymphoblasts ≥5% and up to 25% in bone marrow OR persistent disease-defining cytogenetic abnormality or MRD positive 3. MDS after at least one line of therapy, which includes hypomethylating agent(s) and must be high or very high risk by Revised International Prognostic Scoring System (IPSS-R), monosomy, or complex karyotype or TP53 mutation. 4. In the expansion phase AML patients diagnosed which has been treated with at least two lines of therapy, and refractory or relapsed (CR, CRh or CRi,), including myeloblasts up to 25% OR MRD positive OR persistent disease-defining cytogenetic abnormality OR MRD-negative, but with high- risk disease 3. HLA-A\*02:01 AND HA-1 positive (either H/H or H/R). 4. Suitable for one of the approved conditioning regimens as defined in the protocol. 5. Patient must have an identified donor that is HA 1-negative with 10/10 matched related or unrelated donor
Exclusion criteria
1. Weight \> 100 kg. 2. Prior history of allogeneic stem cell transplantation 3. Prior history of autologous stem cell transplantation within 1 year prior to the planned dosing of BSB-1001 (day 0) 4. Previous genetically engineered chimeric antigen receptor T Cell therapy (CAR-T), approved or investigational, within 2 years of screening, with the exception of patients with ALL previously treated with an autologous CAR-T product. 5. Treatment with other investigational agents within 5 half-lives of the planned dosing of BSB-1001 (day 0). 6. History of treatment with checkpoint inhibitor therapy within 3 months of transplantation. 7. Other malignancy with life expectancy \< 1year. 8. Pregnant or lactating women. 9. Uncontrolled bacterial, viral, or fungal infections at time of enrollment. 10. Past or current viral infections as defined in the protocol. 11. CNS involvement refractory to intrathecal chemotherapy and/or standard cranial- spinal radiation. 12 Karnofsky Performance Score \< 60%. 13\. Inadequate organ function as defined in protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs), including SAEs, GVHD and dose-limiting toxicities | 365 days | Incidence of TEAEs (per Common Terminology Criteria for Adverse Events \[CTCAE\]) |
| Cellular kinetics of BSB-1001 in peripheral blood | 365 days | Quantitation of BSB-1001 (copies per μL of genomic DNA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with relapse | Through 365 days post HSCT | Presence of malignant cells in marrow (\>5%), peripheral blood (\>1%), or extramedullary sites by histopathology after achievement of CR, CRh or CRi at any time after HSCT |
| Incidence of Grades II-IV acute GVHD | Through 100 days post HSCT | Acute GVHD will be graded and assessed for response based on the MAGIC consortium scoring system |
| Incidence of Grades III-IV acute GVHD | Through 100 days post HSCT | Acute GVHD will be graded and assessed for response based on the MAGIC consortium scoring system |
| Time to neutrophil engraftment | Through 365 days post HSCT | Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL |
| Time to platelet engraftment | Through 365 days post HSCT | Time to ≥ 50,000/µL platelets for the first of 3 consecutive days without transfusion |
| Incidence of moderate to severe chronic GVHD | Through 365 days post HSCT | Moderate-to-severe chronic GVHD graded according to NIH scale |
| Overall survival | Through 365 days | Defined as the time from treatment to death due to any cause |
| GVHD-free, relapse-free survival (GFRS) | Through 365 days post HSCT | Defined as time to any of the following events: 1) Grade III-IV aGVHD; 2) chronic GVHD requiring systemic immunosuppression; 3) primary malignancy relapse; or 4) death |
| GVHD-free survival (GFS) | Through 365 days post HSCT | Defined as time to any of the following events: 1) GVHD event or 2) death from any cause |
| Incidence of systemic infections | Through 365 days post HSCT | Defined as infections with a severity of Grades 3 to 5 (as graded by CTCAE v 5.0 or higher) which require treatment with systemic anti-infectives |
Countries
United States
Outcome results
None listed